Dilution factors are a critical component in estimating concentrations of so-called “down-the-drain” chemicals (e.g., pharmaceuticals) in rivers. The present study estimated the temporal and spatial variability of dilution factors around the world using geographically referenced data sets at 0.5° × 0.5° resolution. Domestic wastewater effluents were derived from national per capita domestic water use estimates and gridded population. Monthly and annual river flows were estimated by accumulating runoff estimates using topographically derived flow directions. National statistics, including the median and interquartile range, were generated to quantify dilution factors. Spatial variability of the dilution factor was found to be considerable; for example, there are 4 orders of magnitude in annual median dilution factor between Canada and Morocco. Temporal variability within a country can also be substantial; in India, there are up to 9 orders of magnitude between median monthly dilution factors. These national statistics provide a global picture of the temporal and spatial variability of dilution factors and, hence, of the potential exposure to down-the-drain chemicals. The present methodology has potential for a wide international community (including decision makers and pharmaceutical companies) to assess relative exposure to down-the-drain chemicals released by human pollution in rivers and, thus, target areas of potentially high risk. Environ Toxicol Chem 2014;33:447–452. © 2013 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial, and no modifications or adaptations are made.